Involvement of activating ERK1/2 through G protein coupled receptor 30 and estrogen receptor α/β in low doses of bisphenol A promoting growth of Sertoli TM4 cells

Li Chen Ge, Zhuo Jia Chen, Han Yan Liu, Kun Shui Zhang, Hao Liu, Hong Bin Huang, Ge Zhang, Chris K C WONG, John P. Giesy, Jun Du*, Hong Sheng Wang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

Abstract

Sertoli cells play a pivotal role in supporting proliferation of germ cells and differentiation during spermatogenesis in mammals. Nanomolar concentrations of Bisphenol A (BPA) can significantly stimulate the proliferation of mouse immature Sertoli (TM4) cells. However, mechanisms by which BPA caused these effects were still unclear. In the present study, an inverse U-shaped curve was observed when treating TM4 cells with increasing doses of BPA: 1 to 10. nM BPA significantly stimulated the proliferation of TM4 cells and increased the proportion of cells in S phase; >1. μM BPA caused lesser proliferation of cells. Exposure of TM4 cells to G15 or ICI 182,780, which are specific antagonists of GPR30 and estrogen receptor α/β (ERα/β), respectively, abolished BPA-induced proliferation of cells, which suggests that both GPR30 and ERα/β were involved in the observed effects of BPA. Furthermore, exposure to BPA caused rapid (5. min) activation of ERK1/2 via both GPR30 and ERα/β. Blocking the GPR30/EGFR signal transduction pathway by antagonists suppressed both phosphorylation of ERK and BPA-induced cell proliferation. BPA up-regulated mRNA and protein expression of GPR30 in a concentration-dependent manner. In summary, the results reported here indicated that activating ERK1/2 through GPR30 and ERα/β is involved in low doses of BPA that promoted growth of Sertoli TM4 cells. The GPR30/EGFR/ERK signal is the downstream transduction pathway in BPA-induced proliferation of TM4 Sertoli cells.

Original languageEnglish
Pages (from-to)81-89
Number of pages9
JournalToxicology Letters
Volume226
Issue number1
DOIs
Publication statusPublished - 7 Apr 2014

Scopus Subject Areas

  • Toxicology

User-Defined Keywords

  • Estrogen receptor α/β (ERα/β)
  • GPR30
  • Male
  • Reproduction
  • Sertoli cell
  • TM4

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